Our real-life observational single-center study suggests that MC may provide benefits for some patients with dystonia, particularly those with more widespread or generalized forms of the condition. However, it is important to note that there were several reported side effects associated with MC use, including dry mouth, sedation, dizziness, and psychiatric side effects in some patients. These side effects were manageable in most cases, but did lead to treatment modification in some patients and complete cessation in one patient. It is important to consider the possible mechanisms by which MC might alleviate dystonia. One potential explanation is that the endocannabinoid system, which is abundant in brain areas related to movement control and dystonia such as the basal ganglia and cerebellum, could be involved in the lack of inhibition that leads to excessive muscle contraction in dystonia (17, 18). For example, the CB1 receptor is expressed in GABAergic medium spiny neurons in the striatum and substantia nigra, as well as in glutamatergic cortex projections, all of which play a role in dystonia pathophysiology (19, 20). THC and other cannabinoids have been shown to enhance GABA release and reduce its reuptake while also reducing glutamatergic flow, which could improve movement inhibition (21), as has been suggested in other hyperkinetic movement disorders (22, 23).

Based on our collected data, we sought to identify factors that may impact the perceived improvement in dystonia. Our findings suggest that the spread of dystonia may be a relevant factor to consider. Specifically, patients with focal or segmental dystonia (comprising half of our cohort) reported significantly less benefit compared to those with more widespread dystonia. This observation supports the notion that medication efficacy may vary depending on the type of dystonia. For example, anticholinergics are generally more effective for generalized or segmental dystonias (24, 25). These differences may be related to specific biochemical or physiological mechanisms underlying the pathogenesis of dystonia that should be further investigated. It is important to note, however, that medication efficacy is likely multifactorial and may vary on an individual basis.

Additionally, we observed that the method of administration appeared to be a factor in the perceived improvement of dystonia. Patients who inhaled dried buds reported the greatest improvement, while half of the patients who consumed oil extract reported no improvement in symptoms. Interestingly, most studies on cannabis-based therapies for dystonia have focused on oral consumption (9), with only a few case reports describing the benefit of inhaled MC (26, 27). The difference in reported benefit may be attributed to the pharmacokinetics of cannabinoids. Inhaled THC reaches peak plasma concentration within 8–12 min, while oil extract takes 30 min to reach the first measurable plasma levels and peaks at 3–4 h (28). Furthermore, smoking THC achieves a higher plasma concentration [C(max), (microgram/L) (6)] compared to sublingual oil (29). Nevertheless, it is essential to consider the risks associated with smoking, such as respiratory and vascular complications, when prescribing inhaled cannabis. Overall, our findings suggest that the method of administration should be carefully considered to balance potential benefits with risks.

Our study found that total monthly consumption of MC, THC percentage within the product, and ETDD were positively correlated with perceived benefit in dystonia, indicating a potential role for THC in its treatment. This findings aligns with the increasing use of synthetic THC in other hyperkinetic movement disorders such as tics in Tourette syndrome (30) and Huntington’s disease (31), which has been previously investigated in small data sets. Moreover, previous investigations have also suggested a possible benefit of THC in the treatment of dystonia, which our results support (8, 32).

This study has several limitations that should be considered. The sample size was small and limited by selection bias, as we did not collect data from patients who did not agree to participate. Additionally, all results were based on self-reported measures without objective confirmation and were collected retrospectively at a single point in time without regular follow-up or randomization, which may be subject to false memories and reporting. The retrospective design of this study did not allow for the determination of the time course of the positive response to treatment, nor did it enable the assessment of indirect measures of efficacy, such as a decrease in the use of other drugs. Furthermore, we were unable to elucidate the temporal profile of the response to MC treatment in patients with dystonia, including whether there is a development of tolerance or improvement in the response over the course of MC treatment. Finally, our cohort was diverse, including patients with different etiologies and spreads of dystonia, and using various MC strains with different THC:CBD compositions and from different growers, which may have influenced the results.

To strengthen the evidence for CBM in dystonia, future research should include well-designed randomized double-blind placebo-controlled trials with larger sample sizes to minimize bias and consider placebo effects. Validated motor assessment scales, such as the Burke–Fahn–Marsden dystonia rating scale or the global dystonia severity rating scale, should be used to measure motor symptoms. Specific measures should be incorporated to assess non-motor responses like pain, quality of life, sleep disturbances, and psychiatric symptoms. Additionally, participants should be categorized based on dystonia subtype and etiology to determine if certain subtypes benefit more from CBM treatment. Developing standardized protocols for CBM administration, including dosing regimens, formulations, and administration routes (e.g., inhalation, oral, or sublingual), will enhance consistency and result comparisons. Lastly, comprehensive data collection on adverse events, covering both motor and non-motor side effects, is crucial to understand the safety profile of CBM in dystonia. Implementing these recommendations will establish a strong evidence base for CBM in dystonia, supporting the development of personalized treatment approaches.

In conclusion, our findings indicate that THC-containing MC products may be a promising starting point for further research into the therapeutic benefits of CBM for dystonia in patients with widespread symptoms. However, more randomized, placebo-controlled studies are necessary to determine the most effective THC dose, with or without the addition of CBD and other cannabinoids.